Research Papers:

MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR

Claudia J. Krause, Oliver Popp, Nanthakumar Thirunarayanan, Gunnar Dittmar, Martin Lipp and Gerd Müller _

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Oncotarget. 2016; 7:10414-10432. https://doi.org/10.18632/oncotarget.7248

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Claudia J. Krause1,3, Oliver Popp2, Nanthakumar Thirunarayanan1, Gunnar Dittmar2, Martin Lipp1, Gerd Müller1

1Molecular Tumor Genetics and Immunogenetics, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany

2Mass Spectrometry Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany

3Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Correspondence to:

Gerd Müller, e-mail: [email protected]

Claudia J. Krause, e-mail: [email protected]

Martin Lipp, e-mail: [email protected]

Keywords: KSHV, vGPCR, microRNA-34a, genomic instability, genome maintenance mechanisms

Received: August 13, 2015     Accepted: January 17, 2016     Published: February 8, 2016


The Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded chemokine receptor vGPCR acts as an oncogene in Kaposi’s sarcomagenesis. Until now, the molecular mechanisms by which the vGPCR contributes to tumor development remain incompletely understood. Here, we show that the KSHV-vGPCR contributes to tumor progression through microRNA (miR)-34a-mediated induction of genomic instability. Large-scale analyses on the DNA, gene and protein level of cell lines derived from a mouse model of vGPCR-driven tumorigenesis revealed that a vGPCR–induced upregulation of miR-34a resulted in a broad suppression of genome maintenance genes. A knockdown of either the vGPCR or miR-34a largely restored the expression of these genes and confirmed miR-34a as a downstream effector of the KSHV-vGPCR that compromises genome maintenance mechanisms. This novel, protumorigenic role of miR-34a questions the use of miR-34a mimetics in cancer therapy as they could impair genome stability.

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